Our object in this proposal is to establish the sequential biochemical and morphological events induced by methyl mercury in an isolated neuronal cell population (cerebellar granule cell). Previous studies utilizing synaptosomes revealed a rapid loss of high-energy phosphate accompaaying the mercurial-induced decline in protein synthesis. We will evaluate the hypothesis that methyl mercury exerts a portion of its neurotoxic effect behaving as a K ion ionophore interacting at the cell and/or mitochondrial membrane. Experiments will evaluate the effect of (K ion), valinomycin, ouabain, 86Rb influx/efflux, intracellular (K ion), volume, adenylate energy charge and the magnitude of direct ribosome/mercurial interaction in contributing to the inhibition of protein synthesis. The proposal will provide evidence for early ultrastructural changes occurring in cerebellar granule cells correlated with selected biochemical parameters related to the impairment of protein synthesis. The ultrastructural studies will use quantitative stereologic methodology for analysis of neurotoxicity.